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Culture and Sensitivity
Helping the Infection Preventionist Interpret Antibiograms
Walter Phillips, BS, MS, PhDDirector of MicrobiologyTriStar Healthcare System
Acknowledge
I would like to acknowledge the following contributors to this presentation:
Sheldon Campbell MD, PhD, FCAP Janet Hindler, MCLS MT(ASCP)
Objectives
At the conclusion of this presentation, the participant will be able to: Discuss the purpose of an
antibiogram. Recall the acronym CLSI. Recognize antibiograms for MRSA,
VRE, ESBL and CRE. Define MDRO.
What to Test
CLSI M-100 Sx (where x is an edition number)
Issued yearly, gives guidelines– Keep up!
Don’t report everything– Conform to facility
formulary– Report narrow-spectrum /
inexpensive agents routinely
– Reserve broad-spectrum / expensive agents for resistant isolates
CLSI M100-S24 Table 1A.
Group A
Group B
CLSI M100-S24. Table 1A..
Antimicrobial Susceptibility Testing
Can I use this drug to treat this bug?– With tolerable doses, will enough drug get
to the site of infection to kill the bug? MIC
– Minimal Inhibitory Concentration– broth-based, micro and macro methods
Disc Diffusion E-test
MIC Testing
Liquid media with varying dilutions of antibiotic
Lowest concentration that inhibits growth is the MIC– Minimal Inhibitory
Concentration Various formats available,
automated and non-automated
How to Report
Susceptible, Intermediate, Resistant (S,I, R)
S - means susceptible to usual doses in accessible sites It does NOT mean in the middle of a giant polymicrobial
abscess
I - means susceptible at increased doses or where the drug is concentrated
Usually means a drug to use in urine or if no better choice is available
R - means resistant to usual doses
The S, I, R MIC and disk-zone cutoffs are set by CLSI using epidemiological and pharmacodynamic data.
There may be additional value in some settings to report numerical MICs.
Enterobacteriaceae Cefepime MIC (µg/ml) Breakpoints
AgentOld Breakpoints New Breakpoints
Susc Int Res Susc SDD Res
Cefepime ≤8 16 ≥32 ≤2 4-8 ≥16
CLSI M100-S24. Table 2A.
(13) The interpretive criterion for susceptible is based on a dosage regimen of 1 g every 12 h.
The interpretive criterion for SDD is based on dosing regimens that result in higher cefepime exposure, either higher doses or more frequent doses or both, up to approved maximum dosing regimens.
SDD = “Susceptible Dose Dependent”
clindamycin ≤0.5 S erythromycin ≤0.5 Soxacillin ≤0.5 Spenicillin Rvancomycin ≤0.5 S
Specimen: Wound drainageDiagnosis: Trauma
Staphylococcus aureus
MIC (g/ml)
“Oxacillin-S and penicillin-R staphylococci are susceptible to other anti-staphylococcal ß-lactams (except amoxicillin, ampicillin, and penicillins).”Final Report with Optional
Comment
Specimen: BloodDiagnosis: Severe cellulitis
Staphylococcus aureus
ceftaroline 0.5 Sclindamycin >4 Rdaptomycin 0.5 Sdoxycycline ≤1 Serythromycin >4 Rlinezolid 1 S
oxacillin >8 R penicillin R
rifampin ≤0.5 Strimeth-sulfa ≤0.5/9.5 Svancomycin 2 S
“MRSA are resistant to all β-lactam agents (except ceftaroline). Doxycycline, rifampin or trimeth-sulfa should not be used alone for serious MRSA infections. Ceftaroline, daptomycin and linezolid reported per Dr. Jones request.”
Final Report with Optional Comment
MIC (g/ml)
Newer Antimicrobial Agents for MRSA - Daptomycin
RouteComments
PO IM IV
x
• FDA indications for complicated skin infections, bacteremia
• Disk diffusion does not work; must do MIC
• Susceptible breakpoint only• Resistance uncommon (<1%) but has been
reported• NOT for respiratory infections (lung
surfactant inhibits drug); do not report on respiratory specimens
Zone (mm) MIC (µg/ml)
S I R S I R
- - - ≤1 - -CLSI M100-S24. Table 2C.
Staphylococcus spp.
Newer Antimicrobial Agents for MRSA - Linezolid
RouteComments
PO IM IV
x x
• FDA indications for nosocomial pneumonia, complicated skin infections, uncomplicated skin infections (MSSA); community-acquired pneumonia (MSSA)
• For disk diffusion, examine zone with transmitted light
• Resistance uncommon (<1%) but has been reported
Zone (mm) MIC (µg/ml)
S I R S I R
≥21 - ≤20 ≤4 - ≥8CLSI M100-S24. Table 2C.
Staphylococcus spp.
New Antimicrobial Agents for MRSA - Ceftaroline
RouteComments
PO IM IV
x
• Broad-spectrum cephalosporin (with anti-MRSA activity)
• FDA indications for acute bacterial skin and skin structure infections; community-acquired bacterial pneumonia
• Resistance uncommon (<1%) but has been reported in MRSA
Zone (mm) MIC (µg/ml)
S I R S I R
≥24 21-23
≤20 ≤1 2 ≥4
CLSI M100-S24. Table 2C.
S. aureus
Glycopeptides and Lipopeptides
Major Drugs: Vancomycin, Teicoplanin, Daptomycin
Activity: Gram-positives Resistance Mechanisms: modification
of cell-wall target; increased cell-wall thickness with drug permeability changes, undescribed mechanisms for Daptomycin
Staphylococcus aureus
Major nosocomial and community-acquired pathogen– Responsible for >20% of bacteremia in US/Canada– Transmissible nosocomially and in the community.
Antibiotic resistance -- lots– Methicillin (oxacillin) resistance
Nosocomial Community-acquired
– Vancomycin resistance Relative resistance (VISA) High-level resistance (VRSA)
– Macrolide resistance The D-test
VISA
Vancomycin Intermediate S. aureus– MIC 4-8
Accumulated changes associated with decreased fitness– Thickened cell wall by EM– Mixed large & small colony
morphotypes on plates Associated with poor clinical response
VRSA
MIC ≥8 Acquisition of vanA cluster from
Enterococcus Typically very high MICs, no loss of
fitness– 1st Michigan strain: vanA cluster on a
Staph conjugal plasmid, MIC>1000– PA strain MIC=32 (?loss of cluster or
↓expression)– NY strain MIC=64– 2nd Michigan strain 04/05: MIC >256
VRE
Enterococci are naturally resistant to lots of important antibiotics– Cephalosporin's, SXT, clindamycin– Emerging resistance to penicillin's and vancomycin
Vancomycin resistant enterococci– Van A (E. faecium (most VRE isolates) and E. faecalis)
High level R to Van (> 64 mcg/ml)– Van B (E. faecium and E. faecalis)
Low level R to Van (4-32 mcg/ml) S to teicoplanin
– Van C (Other Enterococcal species) Low level R to Van and S to teicoplanin Not usually transmitted nosocomially
Vancomycin resistance: modified peptidoglycan precursor VRE surveillance cultures
– Routinely screen admissions to selected ICUs: stool or wound sites
Definitions
MDR – multidrug-R (e.g., “NS” to at least 1 drug in ≥ 3 drug
classes) XDR – extensively drug-R
(e.g., “NS” to almost all classes but retains “S” to at least one drug class)
PDR – pandrug-R (e.g., “R” to all drug classes)
Definitions apply to “acquired” (vs. “intrinsic”) resistance and to drugs that might be used to treat an infection caused by the species.
Specimen: Bronchoalveolar lavage Diagnosis: PneumoniaMany Acinetobacter baumannii
amikacin >32 R amp-sulbactam >32 R
cefepime >32 Rceftazidime>32 Rciprofloxacin >2 Rgentamicin >10 Rimipenem >8 Rmeropenem >8 Rpiper-tazobactam 128/4 Rtobramycin >10 Rtrimeth-sulfa >4/76 R
MIC (µg/ml)
What additional
drugs might we be
asked to test?
Specimen: Brochoalveolar lavage Diagnosis: PneumoniaMany Acinetobacter baumannii
amikacin >32 R amp-sulbactam >32 R
cefepime >32 Rceftazidime>32 Rciprofloxacin >2 Rcolistin 1 Sgentamicin >10 Rimipenem >8 Rmeropenem >8 Rminocycline <1 Spiper-tazobactam 128/4 Rtigecycline 1 *tobramycin >10 Rtrimeth-sulfa >4/76 R
MIC (µg/ml)
“Colistin, minocycline and tigecycline
reported per Dr. Jones request. *No standard interpretive criteria
for tigecycline. Infectious Diseases consult suggested.”
Final Report with Optional
Comment
Cephalosporin's and the like
Major Drugs & Major Activities– Narrow Spectrum: Cefazolin, Cephalexin,
Cefalothin; Staph and Strep except MRSA and enterococci; susceptible Gram-negatives
– Expanded Spectrum: Cefoxitin, Cefotetan; Cefuroxime; Cefaclor; add some Gram-negative and anaerobic coverage.
– Broad Spectrum: Ceftriaxone; Cefixime; Ceftazidime; Cefotaxime; much better Gram-negative coverage; less Gram-positive and anaerobic activity. Ceftazidime has excellent Pseudomonas activity.
– Extended Spectrum: Cefipime: better stability to some of the -lactamases
– MRSA-capable: Ceftaroline, effective vs MRSA, retains decent Gram-negative spectrum.
Resistance Mechanisms: an immense variety of -lactamases; altered Penicillin Binding Proteins (PBP).
Extended-Spectrum β-lactamasesESBL
Variants on enzymes found in Enterobacteriaciae, with two nasty properties: – Have broad activity against cephalosporin's
and semisynthetic penicillin's– May not be detected in vitro by typical
susceptibility testing procedures
Outcome data suggests that they do cause treatment failures in vivo.
The phenotypic definition includes inhibition by clavulanic acid.
ESBLS – What To Do?
Change cephalosporin-class, penicillin-class and aztreonam results to R regardless of in vitro result.
Exceptions:– Cephamycins – not hydrolyzed
cefoxitin, cefotetan, cefmetazole– -lactam inhibitor combinations
The inhibitors do inhibit the ESBLs ticarcillin-clavulanate piperacillin-tazobactam
KPC Carbapenemase’s
Associated with outbreaks of multi-resistant Klebsiella pneumoniae, other Enterobacteriaciae, and even Pseudomonas.
Confers resistance to all -lactams, plasmid-borne
Difficult to detect; 12% of isolates test susceptible to imipenem; ertapenem is most sensitive screening drug, or use screening breakpoint of 2 µg/ml with imipenem or meropenem (most-recent guidelines incorporate this change)
Modified Hodge test used to confirm presence of a carbapenemase (not required if using current breakpoints)
Drugs used to treat these isolates include tigecycline and colistin– Poor clinical outcomes
“Routine” Cumulative antibiogramGenerally…one big report, but
increasing emphasis on segregating data to answer
specific questions
Questions?